Microsurgery in rats has made feasible a model for internal diversion of urine into the colon analogous to the ureterosigmoidostomy used in clinical urology. The world-wide use of ureterosigmoidostomy has been discouraged by its chief clinical complications of (a) pyelonephritis and (b) adenocarcinoma of the colon at the anastomotic junction. Both complications are reproduced in the rat model. The proposed research will seek to confirm our pilot experiments indicating a necessary role for the feces in the genesis of both of the complications and focus on the hypothesis that the localized carcinogenesis results from the enzymatic action of fecal bacteria on urinary precarcinogens (e.g., deconjugation, nitro reduction and azoreduction). The preventive value of clinically feasible measures will be investigated including (1) overgrowth of fecal flora with Lactobacillus acidophilus; (2) chronic low-dose urinary antibiotic suppression; (3) urease suppression with acetohydroxamic acid; and (4) beta-glucuronidase inhibition with saccharolactones. Microbiological documentation of aerobes and anaerobes in the colon and kidneys of the rats will be carefully included. Conversely, rats with a diverting colostomy proximal to their ureterosigmoidostomy - a model which did not develop tumors in our pilot experiments - will have infections established in their sigmoid urinary pouch with pure cultures of various fecal bacteria to see if tumors now do develop with defined bacteria and without fecal carcinogens. Careful pathological fixation and examination of the junctional bowel epithelium and of the kidneys will be incorporated into all groups by early autopsies at 2-month intervals during the 12-month observation period. The long term objective is to use the model to define the conditions that bring about "spontaneous" carcinogenesis in such a localized and predictable location and to point to a feasible solution to the clinical complications of ureterosigmoidostomy.